Effect of Metformin Versus Repaglinide Treatment on Glycemic Control and Non-Glycaemic Cardiovascular Risk Factors in Non-Obese Type 2 Diabetic Patients Uncontrolled by Diet
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- HaemoglobinA1c
研究概览
简要总结
Background: Metformin is the first drug of choice in obese patients with type-2 diabetes (T2DM) due to its antiglycaemic as well as its cardiovascular protective potentials. In non-obese T2DM patients insulin-secretagogues are empirically used as first choice. The aim of this study was to evaluate the effect of metformin versus an insulin-secretagogue, repaglinide on glycaemic regulation and non-glycaemic cardiovascular risk markers in non-obese patients with T2DM.
Methods: Single-center, randomised, double-masked, double-dummy, cross-over-study of 96 non-obese (BMI ≤ 27 kg/m2) Caucasian T2DM-patients. After a one month run-in on diet-only treatment, patients were randomised to either repaglinide 2mg three times a day (t.i.d). followed by metformin 1g twice a day (b.i.d.) or vice versa each for a period of four months with a one month wash-out between interventions.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Type-2 diabetes, defined as:
- •Age at onset of diabetes ≥ 40 years
- •Fasting serum C-peptide ≥ 300 pmol/l or a non-fasting or glucagon-stimulated serum C-peptide ≥ 600 pmol/l
- •No history of ketonuria or ketoacidosis.
- •BMI ≤ 27 kg/m
- •Fasting plasma-glucose ≥ 6.5 mmol/l after at least one month of diet-only treatment.
- •HbA1c ≤ 9.5% at ongoing oral anti-hyperglycaemic agents. HbA1c ≥ 6.5% after minimum one month of diet-only treatment.
- •Weight-loss of no more than 5.0 kg during the last 6 months prior to enrolment.
排除标准
- •Type-1 diabetes
- •Insulin-treated type-2 diabetes
- •Secondary diabetes, heart-failure
- •Serum-creatinine above the upper limit
- •Serum-ASAT elevated more than 3 fold above the upper limit
- •Factor II-VII-X decreased below 0.7
- •Ongoing coexisting illnesses with a life-shortening prognosis
- •Mental retardation or reduced intellectual behaviour
- •Pregnancy
- •History of drug-abuse or HbA1c>10.5% at two separate visits with at least one month interval during treatment-periods.
研究组 & 干预措施
4
Metformin plus placebo-Repgalinide. Double-masked, randomized. Duration: Four months.
干预措施: Metformin (Drug)
4
Metformin plus placebo-Repgalinide. Double-masked, randomized. Duration: Four months.
干预措施: Placebo-Repaglinide. (Drug)
2
Repaglinide plus Placebo-Metformin. Double-masked, randomized. Duration: Four months.
干预措施: Repaglinide (Drug)
2
Repaglinide plus Placebo-Metformin. Double-masked, randomized. Duration: Four months.
干预措施: Placebo-Metformin. (Drug)
1
Run-in period: Treatment: Diet-only. Duration: One month.
干预措施: Diet-only. (Other)
3
Wash-out period: Treatment: Diet-only: Duration: One month.
干预措施: Diet-only. (Other)
结局指标
主要结局
HaemoglobinA1c
次要结局
- Waist- and hip-circumference
- Home-monitored 7-point plasma-glucose profiles
- Fasting and postprandial (after a standard test-meal) measures of plasma-glucose, insulin, c-peptide, free fatty acids, lipoproteins, triglycerides and other markers related to lipid-metabolism (e.g. apo-lipoproteins, lipoprotein particle size etc.).
- Platelet aggregation, markers of platelet activity and fibrinolytic markers fasting as well as before and after physical activity.
- Body-weight
- Biomarkers related to inflammation, endothelial dysfunction and fibrinolysis (e.g. hs-CRP, TNF-alpha, IL-6, ICAM, VCAM, E-selectin, vWF, PAI-1 and t-PA, adiponectin, ADMA, AGE-peptides).
- Albuminuria and 24-hour blood-pressure measurements.
- DNA for genotyping.
- Adverse events and safety variables (e.g. hypoglycaemia, haemoglobin, white blood cell count, cobalamine and folate).